Important species differences regarding lymph contribution to gut hormone responses.

Area of Science:

• Endocrinology
• Gastroenterology
• Physiology

Background:

• Glucagon-like peptide-1 (GLP-1) is secreted by the gut post-nutrient intake, stimulating insulin secretion.
• The lymphatic system's role in transporting GLP-1 to systemic circulation before DPP-4 metabolism is unclear.
• Investigating lymphatic transport of GLP-1 is crucial for understanding its bioavailability.

Purpose of the Study:

• To determine the extent of lymphatic system contribution to systemic circulating intact GLP-1.
• To assess if intestinal lymph GLP-1 secretory profiles reflect lamina propria levels before capillary uptake and DPP-4 degradation.

Main Methods:

• Catheterization of portal vein, carotid artery, and cisterna chyli in 7 pigs.
• Infusion of Neuromedin C (NC) with and without a DPP-4 inhibitor (vildagliptin).
• Measurement of total and intact GLP-1 levels and DPP-4 activity.

Main Results:

• Intact and total GLP-1 levels were significantly lower in lymph compared to plasma.
• GLP-1 levels in lymph did not increase upon stimulation, unlike portal vein and carotid artery levels.
• DPP-4 activity was lower in lymph than plasma and further reduced by vildagliptin.

Conclusions:

• The lymphatic system does not appear to transport substantial amounts of intact GLP-1 to the systemic circulation.
• GLP-1 levels in cisternal lymph do not accurately represent hormone levels in the intestinal lamina propria.
• This suggests limited contribution of lymphatic transport to systemic GLP-1 bioavailability.